N.A. Cavara and M. Hollmann (2008).
Shuffling the deck anew: How NR3 tweaks NMDA receptor function.
Molecular Neurobiology 38(1): 16-26.
doi: 10.1007/s12035-008-8029-9
The N-methyl-D-aspartate (NMDA) receptors are the most complex members in the family of ionotropic glutamate receptors. They are involved in long-term potentiation and underlie higher cognitive functions like memory formation and learning. On the other hand, overstimulation of NMDA receptors (NMDARs), leading to a massive influx of Ca2+ ions into the cell, is linked to neurodegenerative disorders such as for example Huntington’s disease and epilepsy. NMDARs are generally considered to be heteromeric tetramers and are conventionally thought to assemble from NR1 splice variants and NR2 subunits, which determine crucial channel properties. With the recent discovery of the functionally different NR3 subunits, many of the known features of NMDARs are being reassessed: The presence of NR3 in NMDARs decreases Mg2+ sensitivity and Ca2+ permeability and reduces agonist-induced current responses. Between altering those essential key characteristics of conventional NMDARs and forming a new class of excitatory glycine receptors when coassembling with NR1, the NR3 subunits give rise to a functionally entirely new array of “NMDA” receptors. Understanding the multifaceted influence of NR3 is imperative to further the understanding of the complex role of NMDARs in neurotransmission and higher brain functions.